The goal of this Phase I proposal is to discover and develop compounds which can release a therapeutically relevant amount of nitric oxide in a controllable manner, formulate them into a hydrogel wound dressing, and demonstrate their ability to promote the healing of diabetic wounds in an in vivo model. To date, development of nitric oxide for these purposes has been hampered by the inability to stably sequester nitric oxide and release it in a controlled and selective way. Traditional treatment with gaseous nitric oxide is impractical due to the cumbersome high pressure gas tanks needed. The work undertaken in this project will: (i) identify novel compounds which stably sequester nitric oxide and only release it when they come in contact with a wound; (ii) formulate these into a suitable hydrogel for delivery to the wound and (iii) identify the proper kinetics of release needed to deliver the appropriate dose of nitric oxide to the wound in vivo. We will prepare several small libraries of compounds (36-45 analogs in total) which release nitric oxide at varying rates when exposed to plasma. These compounds will also be assayed for nitric oxide release, formulated into hydrogels, and tested in a mouse model of diabetic wound healing.